A. V. Litovchenko

Bio: A. V. Litovchenko is an academic researcher from Russian Academy of Sciences. The author has contributed to research in topics: Epilepsy & Apoptosis. The author has co-authored 1 publications.

Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy

Abstract: Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, etc. (multiplex analysis) were studied. In the present work, ultrastructural and immunohistochemical apoptotic signs were found in neurons and oligodendrocytes in the temporal lobe of DRE patients. Levels of proinflammatory cytokines that play a role in apoptosis (TNF-α, FAS, NF-kB) were increased. The blood concentration of IL-4, IL-7, TNF-α is increased and IL-2 is reduced. Oligodendroglial apoptosis has been shown to play an important role in DRE pathogenesis and to explain demyelination. Thus, a comprehensive analysis of revealed changes in the blood and brain in DRE patients showed the neuroinflammation in the epileptic focus, which was combined with the development of apoptosis of glial cells and neurons. This creates conditions for the development of drug resistance and the epilepsy progression.

Markers of Neuroinflammation and Apoptosis in the Temporal Lobe of Patients with Drug-Resistant Epilepsy

Abstract: Current antiepileptic strategies aim to normalize the interaction of the excitatory and inhibitory systems, which is ineffective in treating patients with drug-resistant epilepsy. Neuroinflammatory processes in the epileptic focus and its perifocal area can trigger apoptosis and also contribute to the development of drug resistance. The level of pro- and anti-apoptotic proteins (p-NF-kB, TNF-α, p53, FAS, caspase-3, caspase-9) was analyzed in intraoperative biopsies of the temporal lobe gray and white matter in the brain of patients with drug-resistant epilepsy. An increased level of pro-apoptotic proteins was revealed in the cortex and perifocal area’s white matter against the background of an imbalance of protective anti-apoptotic proteins. It appears that the activation of the extrinsic pathway of apoptosis occurs in the perifocal area, while in the epileptic focus, there are proteins responsible for the activation of the anti-apoptotic survival pathways. Active neuroinflammation in the epileptic focus and perifocal area of the temporal lobe may contribute to the development of the resistance to antiepileptic drugs and the progression of neurodegeneration in such patients.

Glioneuronal apoptosis and neuroinflammation in drug resistant temporal lobe epilepsy

Abstract: The study of glioneuronal apoptosis and neuroinflammation is extremely important for understanding the causes of epilepsy. Currently, the focus is on neuronal apoptosis and certain aspects of neuroinflammation, while glial apoptosis remains poorly understood. Objective : to evaluate neuronal and glial apoptosis in conjunction with neuroinflammation in the area of the epileptic focus in patients with focal drug-resistant epilepsy (DRE). Material and methods . Biopsy specimens of the cortex and white matter of the temporal lobe of the brain from 30 patients with focal DRE due to focal cortical dysplasia were studied. We evaluated pathological changes and structural signs of apoptosis, levels of apoptotic and pro-inflam-matory factors such as caspase-3, caspase-9, FAS, FAS ligand (FAS-L), tumor necrosis factor α (TNFα), p53, nuclear factor κB (NF-κB). Histological methods, transmission electron microscopy (TEM), immunohistochemical study (IHC), and Western blot (WB) were used. The comparison group consisted of 21 people without epilepsy and brain involvement. Results . In DRE patients IHC revealed the expression of active caspase-3 in single neurons (20% of cases) and in gliocytes of the cerebral cortex and white matter (100% of cases). TEM revealed ultrastructural signs of apoptosis in all cases in neurons and oligodendrocytes. The WB of the epileptic focus showed an increased expression of the apoptotic factors caspase-9, FAS, p53 and pro-inflammatory factors TNFα, NF-κB. Conclusion . The results obtained indicate the presence of associated apoptosis and neuroinflammation processes of in DRE. Glial apoptosis is actively involved in epileptogenesis. The main part of apoptotic glia is oligodendrocytes, which explains the well-known phenomenon of myelin damage in epilepsy. Along with neuronal apoptosis, oligodendrocyte apoptosis together with neuroinflammation forms a self-sustaining pathological focus, which contributes to the progression of the disease and the occurrence of relapses.

Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy

Abstract: Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, etc. (multiplex analysis) were studied. In the present work, ultrastructural and immunohistochemical apoptotic signs were found in neurons and oligodendrocytes in the temporal lobe of DRE patients. Levels of proinflammatory cytokines that play a role in apoptosis (TNF-α, FAS, NF-kB) were increased. The blood concentration of IL-4, IL-7, TNF-α is increased and IL-2 is reduced. Oligodendroglial apoptosis has been shown to play an important role in DRE pathogenesis and to explain demyelination. Thus, a comprehensive analysis of revealed changes in the blood and brain in DRE patients showed the neuroinflammation in the epileptic focus, which was combined with the development of apoptosis of glial cells and neurons. This creates conditions for the development of drug resistance and the epilepsy progression.

Two Ferulic Acid Derivatives Inhibit Neuroinflammatory Response in Human HMC3 Microglial Cells via NF-κB Signaling Pathway

Abstract: Various physiological and pathological changes are related to the occurrence and development of neurodegenerative diseases. Neuroinflammation is a major trigger and exacerbation of neurodegenerative diseases. One of the main symptoms of neuritis is the activation of microglia. Thus, to alleviate the occurrence of neuroinflammatory diseases, an important method is to inhibit the abnormal activation of microglia. This research evaluated the inhibitory effect of trans-ferulic acid (TJZ-1) and methyl ferulate (TJZ-2), isolated from Zanthoxylum armatum, on neuroinflammation, by establishing the human HMC3 microglial cell neuroinflammation model induced by lipopolysaccharide (LPS). The results showed both compounds significantly inhibited the production and expression of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) contents, and increased the level of anti-inflammatory factor β-endorphin (β-EP). Furthermore, TJZ-1 and TJZ-2 can inhibit LPS-induced activation of nuclear factor kappa B (NF-κB). It was found that of two ferulic acid derivatives, both had anti-neuroinflammatory effects by inhibiting the NF-κB signaling pathway and regulating the release of inflammatory mediators, such as NO, TNF-α, IL-1β, and β-EP. This is the first report that demonstrates that TJZ-1 and TJZ-2 had inhibitory effects on LPS-induced neuroinflammation in human HMC3 microglial cells, which indicates that two ferulic acid derivates from Z. armatum could be used as potential anti-neuroinflammatory agents.

Epileptic Focus in Drug-Resistant Epilepsy: Structure, Organization, and Pathophysiology

Abstract: The chapter focuses on how different cutting-edge techniques can be used to study electrophysiological, pathomorphological, and biochemical changes in the “epileptic focus” area of the cerebral cortex and white matter to see how epileptic seizures become drug-resistant and how it affects the other regions of the brain. The authors highlight the significance of neuroinflammation and apoptosis in the epilepsy pathogenesis providing EEG characteristics and describing structural changes in the cortex and white matter under such conditions as focal cortical dysplasia and epileptic leukoencephalopathy. Particular focus is given to structural and functional changes in the hippocampus and the role of hippocampal sclerosis in epilepsy. Key conceptions regarding the epileptic focus formation are outlined.

Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model

Abstract: Thalidomide (TAL) has shown potential therapeutic effects in neurological diseases like epilepsy. Both clinical and preclinical studies show that TAL may act as an antiepileptic drug and as a possible treatment against disease development. However, the evidence for these effects is limited. Therefore, the antiepileptogenic and anti-inflammatory effects of TAL were evaluated herein. Sprague Dawley male rats were randomly allocated to one of five groups (n = 18 per group): control (C); status epilepticus (SE); SE-TAL (25 mg/kg); SE-TAL (50 mg/kg); and SE-topiramate (TOP; 60mg/kg). The lithium-pilocarpine model was used, and one day after SE induction the rats received pharmacological treatment for one week. The brain was obtained, and the hippocampus was micro-dissected 8, 18, and 28 days after SE. TNF-α, IL-6, and IL-1β concentrations were quantified. TOP and TAL (50 mg/kg) increased the latency to the first of many spontaneous recurrent seizures (SRS) and decreased SRS frequency, as well as decreasing TNF-α and IL-1β concentrations in the hippocampus. In conclusion, the results showed that both TAL (50 mg/kg) and TOP have anti-ictogenic and antiepileptogenic effects, possibly by decreasing neuroinflammation.